Plasma Concentrations of sTREM-1 as Markers for Systemic Adverse Reactions in Subjects Treated With Weekly Rifapentine and Isoniazid for Latent Tuberculosis Infection.

Tsai-Yu Wang,Chin-Chung Shu,Wei-Juin Su,Wei-Chang Huang,Chung-Yu Chen,Susan Shin-Jung Lee,Yu-Feng Wei,Jia-Yih Feng,Shu-Min Lin,Chih-Bin Lin

doi:10.3389/fmicb.2022.821066

Abstract

BackgroundA regimen of once-weekly rifapentine plus isoniazid for 3 months (3HP) is an effective treatment for subjects with latent tuberculosis infection; however, no reliable biomarker exists for predicting systemic adverse reactions (SARs) to 3HP treatment.MethodsThis prospective, multi-center study evaluated the plasma concentrations of soluble triggering receptors expressed on myeloid cells (sTREM)-1 and sTREM-2 in subjects undergoing 3HP treatment and examined the associations between these biomarkers and SARs.ResultsThis study enrolled 80 consecutive subjects receiving 3HP treatment, 25 of whom had SARs and 55 of whom did not. Subjects with SARs presented higher concentrations of sTREM-1 at baseline than those without SARs (240.1 ± 19.1 vs. 176.7 ± 9.4 pg/mL, P = 0.001). The area under the receiver operating characteristic curves revealed that day 1 plasma levels of sTREM-1 (0.708, 95% CI, 0.584–0.833, P = 0.003) and sTREM-2 (0.343, 95% CI, 0.227–0.459, P = 0.025) as well as the sTREM-1/sTREM-2 ratio (0.748, 95% CI, 0.638–0.858, P = 0.001) had modest discriminative power pertaining to the development of SARs. An sTREM-1 level exceeding the cut-off value (>187.4 pg/mL) (hazard ratio [HR], 6.15; 95% CI 1.67–22.70, P = 0.006) and a sTREM-2 below the cut-off value (<237.2 pg/mL) (HR, 4.46; 95% CI 1.41–14.1, P = 0.011) were independent predictors of SARs after controlling for other variables.ConclusionsPlasma sTREM-1 and sTREM-2 levels are useful biomarkers for predicting SARs during 3HP treatment.Clinical trial governmentNCT04655794

Highlights

Tuberculosis (TB) is the leading cause of infectious diseaseassociated death worldwide, with 9 million new cases and nearly 2 million deaths reported annually (Dye et al, 1999)
The baseline levels of sTREM-1, sTREM-2, sTREM-1/sTREM-2, sTLR4, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were similar in patients with and without autoimmune disease (Supplementary Table 1)
The areas under the Receiver operating characteristic (ROC) curves (AUROCs) revealed that day-1 plasma levels of sTREM-1 (0.708, 95% confidence intervals (CIs), 0.584– 0.833, P = 0.003) and sTREM-2 (0.343, 95% CI, 0.227–0.459, P = 0.025) as well as the sTREM-1/sTREM-2 ratio (0.748, 95% CI, 0.638–0.858, P = 0.001) had modest discriminative power pertaining to the development of systemic adverse reactions (SARs) (Table 3)

Summary

Introduction

Tuberculosis (TB) is the leading cause of infectious diseaseassociated death worldwide, with 9 million new cases and nearly 2 million deaths reported annually (Dye et al, 1999). A regimen of once-weekly rifapentine plus isoniazid for 3 months (3HP) is an effective treatment for patients with LTBI, as the efficacy is similar to that of the 9H regimen but with a shorter treatment duration as well as higher adherence and treatment completion (Sterling et al, 2011). Recent studies have reported that the 3HP regimen is associated with systemic drug reactions (SDRs), such as flu-like syndrome (Sterling et al, 2015). The occurrence of adverse reactions has been reported to be the major cause of treatment discontinuation in patients on the 3HP regimen (Sterling et al, 2011). A regimen of once-weekly rifapentine plus isoniazid for 3 months (3HP) is an effective treatment for subjects with latent tuberculosis infection; no reliable biomarker exists for predicting systemic adverse reactions (SARs) to 3HP treatment

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Conclusion